Disorders of mineral metabolism have been evaluated with methods extending from epidemiology to cellular and molecular biology. Two forms of familial hyperparathyroidism have been characterized in detail. Familial hypocalciuric hypercalcemia is an autosomal dominant trait associated with abnormal interactions with calcium in parathyroid and kidney. Familial multiple endocrine neoplasia type 1 (FMEN1) is an autosomal dominant trait causing hyperfunction of parathyroids, pancreatic islet and anterior pituitary. It is associated with gradual but abnormal proliferation of the tissues affected. Genetic linkage studies in a large kindred have localized the MEN1 gene to the long arm of chromosome 11. Plasma from affected persons shows high mitogenic activity upon cultured bovine parathyroid cells. This mitogenic activity in plasma may contribute to primary hyperparathyroidism in FMEN1. Analysis of blood and parathyroid tumor DNA has revealed that FMEN1 parathyroids often show clonal loss of alleles in the region of the FMEN1 gene on chromosome 11. Thus the FMEN1 gene probably functions as a tumor suppressor gene, analogous to the retinoblastoma gene. Analysis of sporadic parathyroid adenomas revealed that 25% showed allelic loss in a similar region.